Michigan

Halt to research not always good news

The horses are at the mile pole, just an eighth of a mile to go in this year's Kentucky Derby, and has this been a classic horse race!

"Whirlaway is ahead by a length, with War Admiral second, and it seems War Admiral is tiring and fading back. But Citation is coming up strong on the outside to challenge the leaders.

"But wait -- The stewards are stopping the race early for ethical reasons and declaring Whirlaway the winner."

Not a very good way to run a horse race, you would say. But it seems more frequent these days to hear on the news a medical research study was "stopped early for ethical reasons."

On the surface, this seems like a reasonable thing. If two drugs are being compared and the research subjects getting one drug are dying at twice the rate as those getting the other, and the results are statistically significant now, it seems unethical not to continue running the study, risking many more deaths.

For this reason, studies are supposed to have data safety monitoring committees independent of the study investigators. These people snoop into the data at intervals (which the investigators are not supposed to do), and if they see a worrisome trend developing, they can signal a study needs to be stopped.

But there are reasons to suspect stopping early is overused today, when the risk to subjects is minimal.

First, we have the example of our fictitious Kentucky Derby. Just because a drug seems to be in the lead when the study is three-quarters done does not mean that drug would win if the study were completed.

A random cluster of events, good or bad, can make a drug seem like a winner at one point, an outcome that turns out to be only random when you see the whole set of data.

But even more worrisome is an alert issued recently by some Australian doctors, who reviewed recent drug trials stopped early and found 80 percent of them were paid for by drug companies.

The trials were supposed to gather data that would allow a drug to be approved for marketing, and stopping the trial early permitted the drug to get to market sooner.

If the so-called "independent" data safety monitoring committee turned out actually to be under the thumb of the company and its marketing interests, it would not be the first time that type of influence has been exerted in research.

So, if you hear a scientific study has been stopped early, it's not necessarily safe to conclude the "winning" treatment must be a slam-dunk. Determining the truth could end up being a lot more convoluted.

Dr. Howard Brody is director of the Institute for the Medical Humanities at the University of Texas Medical Branch, Galveston.